User:Yuan-Ping Pang/HAB•BoNTAe

Model: Botulinum Neurotoxin Serotype A Endopeptidase Liganded with a Small-Molecule Inhibitor HAB

Botulinum neurotoxin serotype A (BoNTA) causes botulism. Small-molecule inhibitors of BoNTA endopeptidase (BoNTAe) are sought in our laboratories as potential antidotes to antagonize the extracellular or intracellular BoNTA. HAB is one such inhibitor that exhibits nanomolar potency in inhibiting BoNTAe (to be published). Multiple molecular dynamics simulations of HAB•BoNTAe (20 10-ns-long simulations) suggest that one functional group of HAB is highly flexible or intrinsically disordered; the percentages of the top three most-populated conformations of the complex (Models 1-3) are 21%, 13% and 12%, respectively. To evaluate the computational methods used for generating HAB•BoNTAe, the coordinates of the three models were released before the forthcoming crystal structure of HAB•BoNTAe. Only 33% of the heavy atoms of HAB are provided in the released models. The full structure of HAB will be released upon manuscript acceptance.

Download the coordinates of Models 1 (Hab1.pdb), 2 (Hab2.pdb), and 3 (Hab3.pdb) (PDB format)

References & Notes